1) La descarga del recurso depende de la página de origen
2) Para poder descargar el recurso, es necesario ser usuario registrado en Universia


Opción 1: Descargar recurso

Detalles del recurso

Descripción

Although every individual has a unique biology, most medicine still relies on the one-size-fits-all approach, which often fails in the treatment of heterogeneous diseases like cancer. An emerging approach to disease treatment is precision medicine, in which a specific treatment is tailored for individual patients using their biological information, including their genome, phenome, and proteome. Two clinical actions are important for implementing precision medicine in cancer therapies: choosing the correct drugs via patient stratification and choosing a suitable drug dosage and duration via drug response monitoring.

After selecting the potential drug candidate, it is crucial to monitor tumor response to drug therapy because cancer is a dynamic disease that can develop drug resistance. Although non-invasive tumor imaging techniques such as magnetic resonance imaging, computed tomography, and positron emission tomography can assess physical size and metabolic activity of tumors, these techniques have poor time resolution and cannot capture the dynamic changes of bio-molecules implicated with drug resistance. Thus, to effectively monitor drug response, supplemental diagnostic or prognostic markers must be routinely measured from patient biopsies. Unfortunately, routine monitoring of multiple biomarkers from patient biopsies is impractical, as conventional analytical assays require large sample amounts (up to 100-1,000 mg of tissue or 10 mL of blood).

In response to this challenge, this thesis describes the development of various microfluidic technologies that can perform multiplexed measurements (up to 20-plex) using minute amounts of sample (10,000-100,000 cells or 30µL of blood) in a miniaturized analytical platform (maximum 75 × 26 × 1 mm footprint). We applied these technologies for drug screening and drug response monitoring in glioblastoma multiforme, a highly lethal brain tumor, assaying two different types of patient biopsies: cancer cells and blood.

First, we developed an integrated microfluidics-chip/beta particle imaging system that can screen for effective therapies using small amounts of patient-derived cell lines. Since glioblastoma cells have abnormally high glycolytic activity, this was used as a read-out for drug response. Single cells were isolated in micro-traps, and their glycolytic activity was quantitated using a radioactive probe. This platform can assess potential drug targets directly from patient biopsies without administering drugs to the patient.

Second, we developed an in vitro diagnostic test that can monitor tumor drug resistance by measuring up to 14 proteins in finger-prick volumes of blood. This test relies on microfluidics and microarray patterning of antibodies to carry out multiplexed sandwich-type immunofluorescence assays. Using this technology and conventional tumor imaging techniques, we linked proteomic signatures to tumor growth, establishing diagnostic and prognostic models in two clinical treatment cases of bevacizumab and buparlisib. Moreover, we adopted the multiplexed proteomic measurement platform to rapidly screen out small peptide binding agents that target an oncogenic protein in glioblastoma.

The microfluidic tools developed here are sample-efficient and highly informative, and we propose that these techniques could enable routine evaluation of drug response in a precision medicine workflow.


Pertenece a

CaltechTHESIS  

Autor(es)

Kim, Jungwoo - 

Id.: 70082643

Versión: 1.0

Estado: Final

Tipo:  application/pdf - 

Tipo de recurso: Thesis  -  NonPeerReviewed  - 

Tipo de Interactividad: Expositivo

Nivel de Interactividad: muy bajo

Audiencia: Estudiante  -  Profesor  -  Autor  - 

Estructura: Atomic

Coste: no

Copyright: sí

Formatos:  application/pdf - 

Requerimientos técnicos:  Browser: Any - 

Relación: [References] http://resolver.caltech.edu/CaltechTHESIS:09042017-140704721
[References] https://thesis.library.caltech.edu/10411/

Fecha de contribución: 09-may-2018

Contacto:

Localización:
* Kim, Jungwoo (2018) Microfluidic Analysis in Patient Biopsies: toward Precision Medicine for Glioblastoma Multiforme. Dissertation (Ph.D.), California Institute of Technology. doi:10.7907/Z9639MX2. http://resolver.caltech.edu/CaltechTHESIS:09042017-140704721

Otros recursos del mismo autor(es)

  1. Single-cell analysis resolves the cell state transition and signaling dynamics associated with melanoma drug-induced resistance Continuous BRAF inhibition of BRAF mutant melanomas triggers a series of cell state changes that lea...
  2. Development of a high-throughput immunofluorescence assay platform using a DNA-encoded streptavidin library for the rapid evaluation of protein-catalyzed capture agents Protein Catalyzed Capture (PCC) Agents are an emergent class of macrocyclic peptides that selectivel...
  3. High-throughput screening of rare metabolically active tumor cells in pleural effusion and peripheral blood of lung cancer patients Malignant pleural effusion (MPE), the presence of malignant cells in pleural fluid, is often the fir...
  4. Quantitative assessments of glycolysis from single cells The most common positron emission tomography (PET) radio-labeled probe for molecular diagnostics in ...
  5. Single-Cell Phosphoproteomics Resolves Adaptive Signaling Dynamics and Informs Targeted Combination Therapy in Glioblastoma Intratumoral heterogeneity of signaling networks may contribute to targeted cancer therapy resistanc...

Otros recursos de la mismacolección

  1. Regional Structural Geology of Earth and Mars This thesis explores the geologic context around several key environmental transitions on Earth and ...
  2. Synthesis of Functionalized Polymers by Ring-Opening Metathesis Polymerization (ROMP)

    In Chapter 1, the ROMP of 5-methacrylate-1-cyclooctene and the copolymerization of this monomer w...

  3. Tensile Failure and Fracture of Three-Dimensional Brittle Nanolattices The emergence of a new class of cellular solids, i.e., nano- and micro-architected materials, poses ...
  4. An Electrophysiological Study Of Voluntary Movement and Spinal Cord Injury

    Voluntary movement is generated from the interaction between neurons in our brain and the neurons...

  5. Micrometric and Petrofabric Studies of the Val Verde Tonalite, Southern California

    The Val Verde tunnel of the Metropolitan Water District of Southern California, located thirteen ...

Aviso de cookies: Usamos cookies propias y de terceros para mejorar nuestros servicios, para análisis estadístico y para mostrarle publicidad. Si continua navegando consideramos que acepta su uso en los términos establecidos en la Política de cookies.